This invention relates to novel crystalline polymorphic forms of Cipamfylline, and to methods for preparing them.
The capacity to occur in different crystal structures is known as polymorphism and is known to occur in many organic compounds. These different crystalline forms are known as xe2x80x9cpolymorphic modificationsxe2x80x9d or xe2x80x9cpolymorphsxe2x80x9d and are realized in their crystalline state. While polymorphic modifications have the same chemical composition, they differ in packing, geometrical arrangement, and other descriptive properties of the crystalline solid state. As such, these modifications may have different solid-state physical properties such as shape, color density, hardness, deformability, stability, and dissolution properties, etc. Polymorphism of an organic drug molecule and its consequences will be appreciated by the skilled artisan.
Cipamfylline, 1,3-di-cyclopropylmethyl-8-amino xanthine, has the chemical formula C13H17N5O2, m.w. of 275.31, and the following structural formula: 
Its synthesis is described in Example 9, in Maschler et al., Great Britain Patent Application No. 8906792.0 filed on Mar. 23, 1989, in its corresponding EPO patent EP 389282, and corresponding U.S. Pat. No. 5,734,051 whose disclosures are incorporated herein by reference in their entirety.
Cipamfylline is a PDE4 inhibitor and is useful in the treatment, including prophylaxis, of disease states mediated thereby.
Cipamfylline was also disclosed to have TNF inhibiting activity in Esser et al., PCT/US91/08734 (also published as EP 558659), and is therefore useful in the treatment, including prophylaxis of TNF mediated disease states. Suitable assays, dosage forms, and dosage ranges, etc. for the polymorphs of this invention for use in the therapeutic treatment of diseases may be found in either the Maschler et al., or the Esser et al. patent applications whose disclosures are incorporated herein by reference in their entirety.
This invention relates to a novel crystalline polymorph of the 1,3-di-cyclopropylmethyl-8-amino xanthine, referred to hereinafter as Form I, which form of such compound is useful in the treatment of PDE4 or TNF mediated diseases.
This invention also relates to a novel crystalline polymorph of the 1,3-di-cyclopropylmethyl-8-amino xanthine, referred to hereinafter as Form II, which form of such compound is useful in the treatment of PDE4 or TNF mediated diseases.
This invention also relates to a novel crystalline polymorph of the 1,3-di-cyclopropylmethyl-8-amino xanthine, referred to hereinafter as Form IV, which form of such compound is useful in the treatment of PDE4 or TNF mediated diseases.